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tyrosine-protein phosphatase 5, non-receptor type; protein-tyrosine phosphatase striatum-enriched; STEP; neural-specific protein-tyrosine phosphatase (PTPN5)
Function:
- protein-tyrosine phosphatase
- may regulate activity of several effector molecules involved in synaptic plasticity & neuronal cell survival, including MAPKs, Src family kinases, focal adhesion kinase 2, NMDA receptors & AMPA receptors
- phosphorylation at Ser-245 by PKA deactivates PTPN5
- phosphorylation at Thr-255 & Ser-268 by MAPKs stabilizes the phosphatase
- dephosphorylation of these sites results in ubiquitin- mediated degradation of the active phosphatase
Structure:
- belongs to the protein-tyrosine phosphatase family non-receptor class subfamily
- contains 1 tyrosine-protein phosphatase domain
Compartment:
- endoplasmic reticulum membrane
- multi-pass membrane protein (putative)
Alternative splicing: named isoforms=3
Pathology:
- overactive in several neuropsychiatric & neurodegenerative disorders, including Alzheimer's disease
Comparative biology:
- inhibitor of PTPN5/STEP improves cognitive function in a mouse model with no change in beta amyloid or phospho-tau levels [2]
Note:
- uncertain whether Met-1 or Met-25 is the initiator
General
tyrosine phosphatase, non-receptor type
Properties
SIZE: entity length = 565 aa
MW = 64 kD
COMPARTMENT: endoplasmic reticulum
STATE: active state
MOTIF: transmembrane domain {88-108}
transmembrane domain {146-166}
Ser phosphorylation site {S245}
Thr phosphorylation site {T255}
Ser phosphorylation site {S268}
Tyrosine-protein phosphatase {300-555}
MOTIF: binding site
SITE: 461-461
FOR-BINDING-OF: Substrate
Substrate binding {496-502}
cysteine residue {C496}
binding site
SITE: 540-540
FOR-BINDING-OF: Substrate
Database Correlations
OMIM 176879
UniProt P54829
Pfam PF00102
Entrez Gene 84867
ENZYME 3.1.3.48
References
- UniProt :accession P54829
- Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, et al.
Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive
Deficits in a Mouse Model of Alzheimer's Disease.
PLoS Biol (2014) 12(8): e1001923
PMID: 25093460
http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001923